Integrating Peptidomics, Network Pharmacology, Molecular Docking, and In Vitro α-Glucosidase Inhibition Assays to Explore the Hypoglycemic Activity and Action Mechanisms of Chinese Yam Peptides.

Chinese yam possesses anti-type 2 diabetes mellitus (T2DM) potential. However, existing research has focused on its polysaccharides rather than its abundant peptide components. Therefore, this study integrated peptidomics with network pharmacology and molecular docking to explore the potential anti-T2DM mechanisms of Chinese yam peptides. Firstly, this study revealed that crude peptides extracted from Chinese yam possessed a potential hypoglycemic activity, with an IC50 of 568.87 μg/mL against α-glucosidase. Secondly, peptidomics identified 558 peptides with the sequences ranging from 3 to 25 residues. Thirdly, network pharmacology was conducted on 15 candidate peptides selected through bioactivity prediction and safety evaluation. These peptides shared 466 common targets with T2DM, with seven core targets identified through topological network analysis: SRC, EGFR, PTPN11, PIK3R1, ESR1, STAT3, and PIK3CA. Enrichment analysis revealed that these targets were significantly associated with PI3K-Akt and MAPK signaling pathways. Fourthly, molecular docking confirmed the strong binding affinities between the 15 bioactive peptides and seven core targets, particularly the high-affinity binding of peptides SIDLYENRL and RAPDDLDTRL to PIK3CA. Collectively, these findings demonstrate that Chinese yam peptides possess potential hypoglycemic activity and may ameliorate T2DM through the regulation of insulin signaling via PI3K-Akt activation and the modulation of inflammation via the MAPK pathway.